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Escherichia coli K-12 substr. MG1655 Polypeptide: essential cell division protein FtsA



Gene: ftsA Accession Numbers: EG10339 (EcoCyc), b0094, ECK0095

Synonyms: divA

Regulation Summary Diagram: ?

Summary:
FtsA is an essential cell division protein which colocalizes with FtsZ to the septal ring structure; localization is FtsZ-dependent [Ma96b, Addinall96]. Both FtsA and ZipA are required for the recruitment of FtsEX [Schmidt04] and FtsK [Wang98f, Di03], and thus other cell division proteins downstream, to the Z ring. However, premature targeting of cell division proteins to mid-cell allows recruitment of other members of the cell division machinery even in the absence of FtsA [Goehring06]. Localization of FtsA is dependent on the membrane potential [Strahl10].

The FtsA protein belongs to the actin family of ATPases [Kabsch95] and is associated with the cytoplasmic side of the inner membrane [Pla90]. It is well conserved in bacteria, but is conspicuously absent in certain groups such as the mycobacteria, streptomycetes, and cyanobacteria.

Overproduction of FtsA causes inhibition of cell septation [Wang90]. To enable cell division, FtsA and FtsZ have to be present at a ratio of about 1:100 in the cell [Dai92, Dewar92], although this ratio may be closer to 1:10 [Rueda03]. RNase E cleaves the ftsQAZ transcript and decreases the relative abundance of ftsA to ftsZ mRNA [Cam96]. Depletion of RNase E results in an altered FtsA/FtsZ ratio [Tamura06].

FtsA, together with ZipA, supports stabilization of the Z ring [Pichoff02]. A point mutation in FtsA (named FtsA*) can bypass the requirement for ZipA [Geissler03] and FtsK [Geissler05] in cell division and can suppress the temperature sensitivity of the ftsQ1 allele [Geissler05]. FtsA* appears to have an altered interaction with FtsZ [Geissler07] and can partially disassemble FtsZ polymers in vitro [Beuria09]. A point mutation in subdomain 1C of FtsA, ftsA(I143L), can also rescue a variety of divisome assembly defects, including that of ftsK or zipA deletion mutants, as well as localization and recruitment mutations in FtsQ [Goehring07]. Another mutation in subdomain 1C, E124A, suppresses an ftsN deletion mutant and certain other cell division mutants [Bernard07].

FtsA interacts directly with the C-terminal core domain of FtsZ [Wang97d, Ma99]. Residues in FtsA that are required for interaction with FtsZ have been identified [Pichoff07]. The extreme C terminus of FtsA is required for biological activity, localization to the Z ring, and for normal self-interaction [Yim00]. A conserved C-terminal amphipathic helix is required for targeting of FtsA to the membrane and the Z ring [Pichoff05], but appears to serve only as a generic membrane anchor [Shiomi08]. Subdomain 1C is essential for interaction with other FtsA molecules [Carettoni03] and sufficient for recruitment of FtsQ, FtsN and FtsI, but is not required for localization of FtsA to the Z ring [Rico04, Corbin04]. If this subdomain is independently targeted to the Z ring, it can partially suppress an ftsAts mutation; it may therefore constitute an independent domain involved in the recruitment of other septation proteins [Corbin04]. Subdomain 1A is specifically involved in FtsA dimerization, and FtsA self-interaction is important for Z ring assembly [Shiomi07].

In the L form strain LW1655F that lacks peptidoglycan, FtsA carries point mutations in conserved residues [Siddiqui06].

FtsA: "filamentous temperature sensitive A" [Ricard73]

Selected reviews: [Vicente06, Weiss04, Errington03, Buddelmeijer02a]

Citations: [Shen09a, Jimenez11, Pichoff12, Busiek12]

Gene Citations: [Vicente98, Carballes99, MenginLecreulx98, Hara97, Wang91a]

Locations: cytosol, inner membrane

Map Position: [103,982 -> 105,244] (2.24 centisomes)
Length: 1263 bp / 420 aa

Molecular Weight of Polypeptide: 45.33 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0000331 , CGSC:738 , DIP:DIP-47983N , EchoBASE:EB0335 , EcoGene:EG10339 , EcoliWiki:b0094 , ModBase:P0ABH0 , OU-Microarray:b0094 , PortEco:ftsA , PR:PRO_000022714 , Pride:P0ABH0 , Protein Model Portal:P0ABH0 , RefSeq:NP_414636 , RegulonDB:EG10339 , SMR:P0ABH0 , String:511145.b0094 , UniProt:P0ABH0

Relationship Links: InterPro:IN-FAMILY:IPR003494 , InterPro:IN-FAMILY:IPR020823 , Pfam:IN-FAMILY:PF02491 , Smart:IN-FAMILY:SM00842

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0051301 - cell division Inferred from experiment Inferred by computational analysis [UniProtGOA11, Ma96b, Ricard73]
GO:0007049 - cell cycle Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0008360 - regulation of cell shape Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Busiek12, Shen09a, Ebersbach08, Shiomi08, Shiomi07, Karimova05, Pichoff07]
GO:0005524 - ATP binding Inferred from experiment [Beuria09]
GO:0042802 - identical protein binding Inferred from experiment [Ebersbach08, Shiomi08, Karimova05, Shiomi07]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, LopezCampistrou05]
GO:0009898 - cytoplasmic side of plasma membrane Inferred from experiment [Pla90]
GO:0032153 - cell division site Inferred from experiment [Ma96b]

MultiFun Terms: cell processes cell division
cell structure membrane

Essentiality data for ftsA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 1]

Sequence Features

Feature Class Location Citations Comment
Sequence-Conflict 339
[Robinson88, Robinson84, UniProt10a]
Alternate sequence: A → R; UniProt: (in Ref. 1 and 3);


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b0094 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10339; confirmed by SwissProt match.


References

Addinall96: Addinall SG, Lutkenhaus J (1996). "FtsA is localized to the septum in an FtsZ-dependent manner." J Bacteriol 178(24);7167-72. PMID: 8955398

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bernard07: Bernard CS, Sadasivam M, Shiomi D, Margolin W (2007). "An altered FtsA can compensate for the loss of essential cell division protein FtsN in Escherichia coli." Mol Microbiol 64(5);1289-305. PMID: 17542921

Beuria09: Beuria TK, Mullapudi S, Mileykovskaya E, Sadasivam M, Dowhan W, Margolin W (2009). "Adenine nucleotide-dependent regulation of assembly of bacterial tubulin-like FtsZ by a hypermorph of bacterial actin-like FtsA." J Biol Chem 284(21);14079-86. PMID: 19297332

Buddelmeijer02a: Buddelmeijer N, Beckwith J (2002). "Assembly of cell division proteins at the E. coli cell center." Curr Opin Microbiol 5(6);553-7. PMID: 12457697

Busiek12: Busiek KK, Eraso JM, Wang Y, Margolin W (2012). "The early divisome protein FtsA interacts directly through its 1c subdomain with the cytoplasmic domain of the late divisome protein FtsN." J Bacteriol 194(8);1989-2000. PMID: 22328664

Cam96: Cam K, Rome G, Krisch HM, Bouche JP (1996). "RNase E processing of essential cell division genes mRNA in Escherichia coli." Nucleic Acids Res 24(15);3065-70. PMID: 8760895

Carballes99: Carballes F, Bertrand C, Bouche JP, Cam K (1999). "Regulation of Escherichia coli cell division genes ftsA and ftsZ by the two-component system rcsC-rcsB." Mol Microbiol 1999;34(3);442-50. PMID: 10564486

Carettoni03: Carettoni D, Gomez-Puertas P, Yim L, Mingorance J, Massidda O, Vicente M, Valencia A, Domenici E, Anderluzzi D (2003). "Phage-display and correlated mutations identify an essential region of subdomain 1C involved in homodimerization of Escherichia coli FtsA." Proteins 50(2);192-206. PMID: 12486713

Corbin04: Corbin BD, Geissler B, Sadasivam M, Margolin W (2004). "Z-ring-independent interaction between a subdomain of FtsA and late septation proteins as revealed by a polar recruitment assay." J Bacteriol 186(22);7736-44. PMID: 15516588

Dai92: Dai K, Lutkenhaus J (1992). "The proper ratio of FtsZ to FtsA is required for cell division to occur in Escherichia coli." J Bacteriol 174(19);6145-51. PMID: 1400163

Dewar92: Dewar SJ, Begg KJ, Donachie WD (1992). "Inhibition of cell division initiation by an imbalance in the ratio of FtsA to FtsZ." J Bacteriol 174(19);6314-6. PMID: 1400183

Di03: Di Lallo G, Fagioli M, Barionovi D, Ghelardini P, Paolozzi L (2003). "Use of a two-hybrid assay to study the assembly of a complex multicomponent protein machinery: bacterial septosome differentiation." Microbiology 149(Pt 12);3353-9. PMID: 14663069

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Ebersbach08: Ebersbach G, Galli E, Moller-Jensen J, Lowe J, Gerdes K (2008). "Novel coiled-coil cell division factor ZapB stimulates Z ring assembly and cell division." Mol Microbiol 68(3);720-35. PMID: 18394147

Errington03: Errington J, Daniel RA, Scheffers DJ (2003). "Cytokinesis in bacteria." Microbiol Mol Biol Rev 67(1);52-65. PMID: 12626683

Geissler03: Geissler B, Elraheb D, Margolin W (2003). "A gain-of-function mutation in ftsA bypasses the requirement for the essential cell division gene zipA in Escherichia coli." Proc Natl Acad Sci U S A 100(7);4197-202. PMID: 12634424

Geissler05: Geissler B, Margolin W (2005). "Evidence for functional overlap among multiple bacterial cell division proteins: compensating for the loss of FtsK." Mol Microbiol 58(2);596-612. PMID: 16194242

Geissler07: Geissler B, Shiomi D, Margolin W (2007). "The ftsA* gain-of-function allele of Escherichia coli and its effects on the stability and dynamics of the Z ring." Microbiology 153(Pt 3);814-25. PMID: 17322202

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Goehring06: Goehring NW, Gonzalez MD, Beckwith J (2006). "Premature targeting of cell division proteins to midcell reveals hierarchies of protein interactions involved in divisome assembly." Mol Microbiol 61(1);33-45. PMID: 16824093

Goehring07: Goehring NW, Petrovska I, Boyd D, Beckwith J (2007). "Mutants, suppressors, and wrinkled colonies: Mutant alleles of the cell division gene ftsQ point to functional domains in FtsQ and a role for domain 1C of FtsA in divisome assembly." J Bacteriol 189(2):633-45. PMID: 16980443

Hara97: Hara H, Yasuda S, Horiuchi K, Park JT (1997). "A promoter for the first nine genes of the Escherichia coli mra cluster of cell division and cell envelope biosynthesis genes, including ftsI and ftsW." J Bacteriol 179(18);5802-11. PMID: 9294438

Jimenez11: Jimenez M, Martos A, Vicente M, Rivas G (2011). "Reconstitution and organization of Escherichia coli proto-ring elements (FtsZ and FtsA) inside giant unilamellar vesicles obtained from bacterial inner membranes." J Biol Chem 286(13);11236-41. PMID: 21257762

Kabsch95: Kabsch W, Holmes KC (1995). "The actin fold." FASEB J 9(2);167-74. PMID: 7781919

Karimova05: Karimova G, Dautin N, Ladant D (2005). "Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis." J Bacteriol 187(7);2233-43. PMID: 15774864

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Ma96b: Ma X, Ehrhardt DW, Margolin W (1996). "Colocalization of cell division proteins FtsZ and FtsA to cytoskeletal structures in living Escherichia coli cells by using green fluorescent protein." Proc Natl Acad Sci U S A 93(23);12998-3003. PMID: 8917533

Ma99: Ma X, Margolin W (1999). "Genetic and functional analyses of the conserved C-terminal core domain of Escherichia coli FtsZ." J Bacteriol 181(24);7531-44. PMID: 10601211

MenginLecreulx98: Mengin-Lecreulx D, Ayala J, Bouhss A, van Heijenoort J, Parquet C, Hara H (1998). "Contribution of the Pmra promoter to expression of genes in the Escherichia coli mra cluster of cell envelope biosynthesis and cell division genes." J Bacteriol 180(17);4406-12. PMID: 9721276

Pichoff02: Pichoff S, Lutkenhaus J (2002). "Unique and overlapping roles for ZipA and FtsA in septal ring assembly in Escherichia coli." EMBO J 21(4);685-93. PMID: 11847116

Pichoff05: Pichoff S, Lutkenhaus J (2005). "Tethering the Z ring to the membrane through a conserved membrane targeting sequence in FtsA." Mol Microbiol 55(6);1722-34. PMID: 15752196

Pichoff07: Pichoff S, Lutkenhaus J (2007). "Identification of a region of FtsA required for interaction with FtsZ." Mol Microbiol 64(4);1129-38. PMID: 17501933

Pichoff12: Pichoff S, Shen B, Sullivan B, Lutkenhaus J (2012). "FtsA mutants impaired for self-interaction bypass ZipA suggesting a model in which FtsA's self-interaction competes with its ability to recruit downstream division proteins." Mol Microbiol 83(1);151-67. PMID: 22111832

Pla90: Pla J, Dopazo A, Vicente M (1990). "The native form of FtsA, a septal protein of Escherichia coli, is located in the cytoplasmic membrane." J Bacteriol 172(9);5097-102. PMID: 2203741

Ricard73: Ricard M, Hirota Y (1973). "Process of cellular division in Escherichia coli: physiological study on thermosensitive mutants defective in cell division." J Bacteriol 116(1);314-22. PMID: 4583216

Rico04: Rico AI, Garcia-Ovalle M, Mingorance J, Vicente M (2004). "Role of two essential domains of Escherichia coli FtsA in localization and progression of the division ring." Mol Microbiol 53(5);1359-71. PMID: 15387815

Robinson84: Robinson AC, Kenan DJ, Hatfull GF, Sullivan NF, Spiegelberg R, Donachie WD (1984). "DNA sequence and transcriptional organization of essential cell division genes ftsQ and ftsA of Escherichia coli: evidence for overlapping transcriptional units." J Bacteriol 160(2);546-55. PMID: 6094474

Robinson88: Robinson AC, Begg KJ, Sweeney J, Condie A, Donachie WD (1988). "Mapping and characterization of mutants of the Escherichia coli cell division gene, ftsA." Mol Microbiol 2(5);581-8. PMID: 2846985

Rueda03: Rueda S, Vicente M, Mingorance J (2003). "Concentration and assembly of the division ring proteins FtsZ, FtsA, and ZipA during the Escherichia coli cell cycle." J Bacteriol 185(11);3344-51. PMID: 12754232

Schmidt04: Schmidt KL, Peterson ND, Kustusch RJ, Wissel MC, Graham B, Phillips GJ, Weiss DS (2004). "A predicted ABC transporter, FtsEX, is needed for cell division in Escherichia coli." J Bacteriol 186(3);785-93. PMID: 14729705

Shen09a: Shen B, Lutkenhaus J (2009). "The conserved C-terminal tail of FtsZ is required for the septal localization and division inhibitory activity of MinC(C)/MinD." Mol Microbiol 72(2);410-24. PMID: 19415799

Shiomi07: Shiomi D, Margolin W (2007). "Dimerization or oligomerization of the actin-like FtsA protein enhances the integrity of the cytokinetic Z ring." Mol Microbiol 66(6);1396-415. PMID: 17986188

Shiomi08: Shiomi D, Margolin W (2008). "Compensation for the loss of the conserved membrane targeting sequence of FtsA provides new insights into its function." Mol Microbiol 67(3);558-69. PMID: 18186792

Siddiqui06: Siddiqui RA, Hoischen C, Holst O, Heinze I, Schlott B, Gumpert J, Diekmann S, Grosse F, Platzer M (2006). "The analysis of cell division and cell wall synthesis genes reveals mutationally inactivated ftsQ and mraY in a protoplast-type L-form of Escherichia coli." FEMS Microbiol Lett 258(2);305-11. PMID: 16640589

Strahl10: Strahl H, Hamoen LW (2010). "Membrane potential is important for bacterial cell division." Proc Natl Acad Sci U S A 107(27);12281-6. PMID: 20566861

Tamura06: Tamura M, Lee K, Miller CA, Moore CJ, Shirako Y, Kobayashi M, Cohen SN (2006). "RNase E maintenance of proper FtsZ/FtsA ratio required for nonfilamentous growth of Escherichia coli cells but not for colony-forming ability." J Bacteriol 188(14);5145-52. PMID: 16816186

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Vicente06: Vicente M, Rico AI (2006). "The order of the ring: assembly of Escherichia coli cell division components." Mol Microbiol 61(1);5-8. PMID: 16824090

Vicente98: Vicente M, Gomez MJ, Ayala JA (1998). "Regulation of transcription of cell division genes in the Escherichia coli dcw cluster." Cell Mol Life Sci 54(4);317-24. PMID: 9614967

Wang90: Wang HC, Gayda RC (1990). "High-level expression of the FtsA protein inhibits cell septation in Escherichia coli K-12." J Bacteriol 172(8);4736-40. PMID: 2198274

Wang91a: Wang XD, de Boer PA, Rothfield LI (1991). "A factor that positively regulates cell division by activating transcription of the major cluster of essential cell division genes of Escherichia coli." EMBO J 1991;10(11);3363-72. PMID: 1915297

Wang97d: Wang X, Huang J, Mukherjee A, Cao C, Lutkenhaus J (1997). "Analysis of the interaction of FtsZ with itself, GTP, and FtsA." J Bacteriol 179(17);5551-9. PMID: 9287012

Wang98f: Wang L, Lutkenhaus J (1998). "FtsK is an essential cell division protein that is localized to the septum and induced as part of the SOS response." Mol Microbiol 29(3);731-40. PMID: 9723913

Weiss04: Weiss DS (2004). "Bacterial cell division and the septal ring." Mol Microbiol 54(3);588-97. PMID: 15491352

Yim00: Yim L, Vandenbussche G, Mingorance J, Rueda S, Casanova M, Ruysschaert JM, Vicente M (2000). "Role of the carboxy terminus of Escherichia coli FtsA in self-interaction and cell division." J Bacteriol 182(22);6366-73. PMID: 11053380

Other References Related to Gene Regulation

Aldea90: Aldea M, Garrido T, Pla J, Vicente M (1990). "Division genes in Escherichia coli are expressed coordinately to cell septum requirements by gearbox promoters." EMBO J 1990;9(11);3787-94. PMID: 1698623

Ballesteros98: Ballesteros M, Kusano S, Ishihama A, Vicente M (1998). "The ftsQ1p gearbox promoter of Escherichia coli is a major sigma S-dependent promoter in the ddlB-ftsA region." Mol Microbiol 1998;30(2);419-30. PMID: 9791185

Dyszel10: Dyszel JL, Soares JA, Swearingen MC, Lindsay A, Smith JN, Ahmer BM (2010). "E. coli K-12 and EHEC genes regulated by SdiA." PLoS One 5(1);e8946. PMID: 20126629

Eraso14: Eraso JM, Markillie LM, Mitchell HD, Taylor RC, Orr G, Margolin W (2014). "The Highly Conserved MraZ Protein Is a Transcriptional Regulator in Escherichia coli." J Bacteriol 196(11);2053-66. PMID: 24659771

Gohler11: Gohler AK, Kokpinar O, Schmidt-Heck W, Geffers R, Guthke R, Rinas U, Schuster S, Jahreis K, Kaleta C (2011). "More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli." BMC Syst Biol 5(1);197. PMID: 22168595

Ishino89: Ishino F, Jung HK, Ikeda M, Doi M, Wachi M, Matsuhashi M (1989). "New mutations fts-36, lts-33, and ftsW clustered in the mra region of the Escherichia coli chromosome induce thermosensitive cell growth and division." J Bacteriol 171(10);5523-30. PMID: 2676977

Sitnikov96: Sitnikov DM, Schineller JB, Baldwin TO (1996). "Control of cell division in Escherichia coli: regulation of transcription of ftsQA involves both rpoS and SdiA-mediated autoinduction." Proc Natl Acad Sci U S A 1996;93(1);336-41. PMID: 8552633

Vinella93: Vinella D, Joseleau-Petit D, Thevenet D, Bouloc P, D'Ari R (1993). "Penicillin-binding protein 2 inactivation in Escherichia coli results in cell division inhibition, which is relieved by FtsZ overexpression." J Bacteriol 175(20);6704-10. PMID: 8407846

Vinella93a: Vinella D, Bouloc P, D'Ari R (1993). "GTPase enters the ring." Curr Biol 3(1);65-6. PMID: 15335888

Yamamoto01a: Yamamoto K, Yata K, Fujita N, Ishihama A (2001). "Novel mode of transcription regulation by SdiA, an Escherichia coli homologue of the quorum-sensing regulator." Mol Microbiol 41(5);1187-98. PMID: 11555297


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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